Potassium Phosphate, Tribasic → 5-(2,4-Difluorophenoxy)-6-{6-methyl-1-[(4-methylphenyl)sulfonyl]-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 629296Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 629296
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[C:5]2[CH:17]=[CH:18][N:19]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:4]=2[C:3]1=[O:30].Br[C:32]1[C:41]([O:42][C:43]2[CH:48]=[CH:47][C:46]([F:49])=[CH:45][C:44]=2[F:50])=[CH:40][C:35]2[NH:36][C:37](=[O:39])[NH:38][C:34]=2[CH:33]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC12CC3(C)OC(C)(CC(C)(O3)O1)P2C1C=CC=CC=1>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:50][C:44]1[CH:45]=[C:46]([F:49])[CH:47]=[CH:48][C:43]=1[O:42][C:41]1[C:32]([C:6]2[C:5]3[CH:17]=[CH:18][N:19]([S:20]([C:23]4[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=4)(=[O:22])=[O:21])[C:4]=3[C:3](=[O:30])[N:2]([CH3:1])[CH:7]=2)=[CH:33][C:34]2[NH:38][C:37](=[O:39])[NH:36][C:35]=2[CH:40]=1

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 534277901,3,5,7-Tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantaneHCID 867210626-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-oneHCID 1180936705-Bromo-6-(2,4-difluorophenoxy)-1,3-dihydro-2H-benzimidazol-2-one

Produkt 1

HCID 1180936395-(2,4-Difluorophenoxy)-6-{6-methyl-1-[(4-methylphenyl)sulfonyl]-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl}-1,3-dihydro-2H-benzimidazol-2-oneAusbeute 21,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A suspension of 6-methyl-1-[(4-methylphenyl)sulfonyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (85.0 mg, 0.20 mmol), 5-bromo-6-(2,4-difluorophenoxy)-1,3-dihydro-2H-benzimidazol-2-one (74.5 mg, 0.218 mmol), potassium phosphate (0.10 g, 0.50 mmol), tris(dibenzylideneacetone)dipalladium (O) (5.0 mg, 0.006 mmol), and 1,3,5,7-tetramethyl-8-phenyl-2,4,6-trioxa-8-phosphatricyclo[3.3.1.13,7]decane (6.8 g, 0.0232 mmol) in 1,4-dioxane (2 mL) and water (0.4 mL) was degassed with nitrogen for 5 min and stirred at 80° C. for 1 h. The reaction mixture was diluted with ethyl acetate and water and filtered over celite. The organic layer was separated, washed with brine, dried with magnesium sulfate, filtered, and concentrated to give a crude residue. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min) gave the desired product (24 mg, 18%) as an off-white foam. LCMS calculated for C28H21F2N4O5S (M+H)+: m/z=563.1. found: 563.1.

Aufarbeitung

  1. customwas degassed with nitrogen for 5 min
  2. additionThe reaction mixture was diluted with ethyl acetate and water
  3. filtrationfiltered over celite
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a crude residue
  10. customPurification via preparative LCMS (XBridge C18 column
  11. washeluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min)

Quellen und Nachweise

ORD-Eintrag
ord-66162bd552c743e98e6734d5956726f6
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315501B2

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